Human fetal hemoglobin (HbF) has a weaker affinity for 2,3 diphosphoglyceric acid than HbA and has other characteristics, such as non-participation in gel formation with HbS, that distinguish if from HbA. The molecular basis of these differences is not clear. HbF contains two alpha chains and two gamma chains instead of the two alpha chains and two beta chains of HbA. As a result there are 39 amino acid differences between HbF and HbA, several of which are in the 2,3 diphosphoglyceric acid binding site. A number of others are clustered in one exposed helical region of the gamma chain. We are using solid phase synthetic methods to reproduce this helical region. Immunoabsorption of an antiserum to HbF will then be used in an attempt to obtain non-precipitating antibodies specific for this region which do not crossreact with HbA. A radioimmunoassay using (c14)-carbamoylated HbF will be used to assess the specificity of binding. We have also obtained crystals of HbF of suitable size for X-ray diffraction studies. The specific antibodies and X-ray studies will give information on the conformational and surface structural characteristics of HbF. In addition the antibodies may be useful in quantitating small amounts of HbF in standard laboratory procedures and in prenatal diagnosis of hemoglobinopathies.